The objective of this proposal is to characterize certain proteins and/or biologic activities tending to co-precipitate in fibronectin (CIg)-rich plasma fractions. The applicants propose to develop an efficient, potentially large-scale method for separating one of these biologic activities, known as the factor VIII complex, from another activity (i.e., promoting opsonic activity of macrophages) associated with fibronectin. We intend to exploit the recent finding that heparin can bind and efficiently precipitate plasma fibronectin as the so-called heparin-precipitable fraction (HPF). We will first determine whether the factor VIII complex also is precipitated in the HPF or whether it remains in the supernatant plasma. Further purification strategy will be based upon the results of these analyses. Other heparin-like materials without appreciable anticoagulant activity will also be studied (e.g., "low affinity" heparin, heparan sulfate). Existing methodologies for preparation of factor VIII concentrates (i.e., cryoprecipitate, "intermediate" and "high purity" concentrates) will be evaluated with respect to fractional distribution of the various proteins and biologic activities within them. The results could lead to a method for effective separation of the factor VIII complex from other non-related biologic activities, and could also result in a simple and perhaps more efficient method for increasing the specific activity of factor VIII concentrates.